Rheumatological diseases affect a large sector of the population and lead to chronic pain, disability, reduced quality of life, and in many cases, shortened life span. The monetary costs are huge with respect to lost earnings, as well as direct health care costs.

The Rheumatology Department strives to augment its clinical rheumatology services with research programs into the epidemiology, causation and complications of rheumatic diseases (“bedside to bench”), coupled with the evaluation of new generations of pharmaceutical agents for the treatment of arthritis (“bench to bedside”). These rheumatic diseases include Sjögren’s syndrome, giant cell arteritis, osteoarthritis, scleroderma, rheumatoid arthritis, ankylosing spondylitis, gout, and fibromyalgia.

We are always looking for exceptional students to participate in our research projects. Please contact Sue Lester for more information.

Polymyalgia rheumatica (PMR) is an inflammatory syndrome with pain or stiffness, usually in the neck, shoulders, upper arms, and hips, but which may occur all over the body. The aim of this project is to perform a systematic review of the epidemiology of PMR and to determine the epidemiology, clinical features and management of PMR in Australia, using available Australian General Practice Data.

The North West Adelaide Health Study (NWAHS) is a representative biomedical population cohort study of approximately 4000 adults aged 18 years and over recruited from the northern and western regions of Adelaide. The study was designed to assess the prevalence of priority conditions and to inform policy decisions about health care provision in South Australia, and NWAHS Stage 2 data collection specifically focused on information relating to musculoskeletal conditions. The aim of this project is to determine healthcare utilisation in patients with chronic musculoskeletal conditions, using NWAHS data integrated with Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data.

Glucocorticoids (GC) are a class of steroid hormones with immunosuppressive and anti-inflammatory effects. However, they are also associated with a number of side effects. While the treating clinician may focus on the most clinically serious GC related adverse effects, such as an increased risk of cardiovascular disease, diabetes and bone density loss, little is known about the patient perspective of the impact of GC treatment. The aim of this project is to develop a question to measure the impact of GC treatment from a patient perspective. These types of patient reported outcome measures (PROM) are a new era in clinical research which will enable more patient-centred treatment decisions.

Symptoms include severe dryness of the eyes and mouth, rampant dental decay, fatigue, muscle and joint pains, in addition to a variety of other symptoms. pSS may be a serious disease, with excess mortality caused by haematological cancer, which is presumed due to immune dysregulation. The majority of patients with pSS have anti-nuclear autoantibodies (ANA) which are related to systemic inflammation and more severe disease, but their association with cancer risk is not known. While ANA are common in patients across a range of systemic autoimmune diseases, a subgroup of these autoantibodies, anti-Ro (SSA) and anti-La (SSB) are most common in patients with pSS.
The aim of this project is to determine cancer risk (and cancer type) and mortality associated with ANA autoantibody subclasses in South Australia.
ANA autoantibody positive patients will be ascertained from SA Pathology autoantibody testing results over the last 10 years, and divided into 3 groups:

anti-Ro + La positive

anti-Ro only positive and

ANA positive, but negative for anti-Ro or anti-La.

Data will be linked to the South Australian Cancer Registry and Birth and Deaths Registry. Standardised cancer incidence and mortality ratios will be calculated using South Australian population data as the reference. This project is suitable for Masters project or as part of a PhD project.

Autoantibody-formed immune complexes have long been implicated in mechanisms of systemic autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and primary Sjogren’s Syndrome (pSS).

Evidence suggests that mechanisms relate to the activation of pattern recognition receptors (PPR) of the innate immune system whereby these immune complexes, which contain nuclear components, mimic the effects of microbial pathogen DNA/RNA. We have established an association between the presence of anti-Ro (SS-A) and anti-La (SS-B) autoantibodies in pSS patients, and elevated levels of cytokines from both the families of IL-1 (IL-1beta and IL-18) and IFN-I (IFN-alpha) in their sera. These cytokines are indicative of inflammasome activation, which are one group innate immune pattern recognition receptors. While inflammasome activation is well studied in immune cells, there is increasing interest in the role of inflammasomes in epithelial cells and therefore immune defence at mucosal surfaces. This is of particular relevance to pSS where inflammasome activation may be related to salivary gland destruction in pSS. The aim of this project is to determine if anti- nuclear autoantibody immune complexes activate the inflammasome in epithelial cells and monocytes. This project is suitable for an Honours project or as part of a PhD project.

Primary Sjögren’s Syndrome (SS) is a chronic, autoimmune inflammatory disease which is characterized by lymphocytic infiltration of the salivary and lacrimal glands, resulting in abnormal tear and saliva secretion.

Autoantibodies against nucleolar components Ro and La are also frequently present. There is substantial evidence that interferons (IFNs) play significant roles in the pathogenesis of rheumatic diseases, including pSS, which is manifest as the so-called “interferon signature”. The mechanism of IFN activation relates to the activation of pattern recognition receptors (PPR) of the innate immune system whereby autoantibody immune complexes, which contain nuclear components, mimic the effects of microbial pathogen DNA/RNA. However, there is striking heterogeneity in IFN activity amongst different individuals and diseases, and the frequency and clinical associations of the different patterns are unclear. The aim of this project is to characterise the IFN signature in both the serum and salivary glands of pSS patients, using a combination of qPCR and immunoblotting techniques, and to determine the associations with serology, disease activity and clinical features. This project is suitable for an Honours project or as part of a PhD project.

“A randomised trial of colchicine for osteoarthritis of the hand” (COLAH)

Hand osteoarthritis is very common amongst older Australians and results in severe impairment in daily living activities for many people. There are currently few treatments available. This trial is testing a medication called colchicine, typically prescribed for acute treatment of joint paint in gout, for the treatment of osteoarthritis in the hand.

The Australasian Arthritis Genomics Recruitment Collaborative: Infrastructure for establishing a quality clinical resource for genetic research

Project Grant

$50,000

2011

International

A/Prof Rischmueller and Sue Lester have an on-going international collaborations with both SGENE and SLEGEN which are international consortia to research genetic associations with Sjðgren’s syndrome and systemic lupus erythematosus respectively. SGENE has already published the first genome wide association study for Sjðgren’s syndrome (in Nature Genetics in November 2012) and patient recruitment is ongoing with the aim of studying the genetics of lymphoma risk. In 2014, SGENE and SLEGEN have combined to publish finer mapping of the associations for the IRF5-TNOP3 region, a common suceptibility region for both diseases

A/Prof Rischmueller, A/Prof Hill and Sue Lester have an on-going collaboration with the Australasian Genomics Recruitment Initiative in Australasia (AGRIA), which is collecting samples from Australia and New Zealand for genetic studies of Giant Cell Arteritis, gout and ankylosing spondylitis, with Sjögren’s syndrome to be added in 2015. The Giant Cell Arteritis component is funded by a current NHMRC grant. This has an international collaboration with Prof Ann Morgan (Leeds), Tony Merriman (Otago) and Javier Martin (Spain).

National

A/Prof Rischmueller has an on-going with Dr Fabien Vincent and Professor Fabienne Mackay (Immunology department, B lymphocyte, BAFF and Autoimmunity Laboratory, Alfred Medical Research and Education Precinct) and Professor Eric Morand (Head of the Lupus Clinic at Southern Health/Monash Medical centre) to investigate, and compare, the role of TACI variants in Sjögren’s syndrome and systemic lupus erythematosus phenotypes, B cell subsets and type I interferon expression in plasmacytoid dendritic cells.

A/Prof Rischmueller, A/Prof Hill and Sue Lester are collaborators with the Australian Scleroderma Interest Group (ASIG) which currently consists of a clinical database of over 1500 patients and a biobank, which is housed at the Basil Hetzel Institute. An Immunochip genome wide association study for this cohort was published in 2014 which identified several novel associations.